The prognostic value and potential immunotherapeutic efficacy of ACVR1 in treating gastric cancer.

BACKGROUND: The discovery of biomarkers has facilitated the treatment of cancer. At present, the relationship between activin A receptor type-1 ( ACVR1 ) and gastric cancer is gradually discovered. The aim of this study was to explore the expression of ACVR1 in gastric cancer and its clinical significance, to study the relationship between ACVR1 and tumor microenvironment (TME) for the prognosis of gastric cancer, and to further identify new targets for immunotherapy in gastric cancer.

METHODS: ACVR1 was first selected as a study gene according to several cancer and gastric cancer public datasets. Its pancancer expression was explored using the UCSC Xena database. The expression level, prognosis, and clinicopathological features of ACVR1 in gastric cancer were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemistry (IHC)-based experiments were conducted to study the expression of ACVR1 at the protein level. The IHC data were analyzed for correlations between ACVR1 expression and various clinicopathological factors and prognosis. The correlation of this gene with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, immune checkpoints, drug therapy, tumor mutation burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) system was analyzed using R software.

RESULTS: TCGA data showed that the expression of ACVR1 was higher in gastric cancer tissues than in paracancerous tissues. Moreover, the IHC experiments indicated that ACVR1 was upregulated in gastric cancer tissues at the protein level. Both univariate Cox and multivariate Cox results showed that the increase of ACVR1 was closely associated with tumor stage, size, lymph node metastasis, and age. High ACVR1 expression was linked to a poor prognosis of gastric cancer. The results also revealed that ACVR1 was closely related to suppressive immune cells and pathways. Analyses of immune checkpoints, antitumor drug, TMB, and immune microenvironment indicated that ACVR1 had an antitumor immune effect, promoting gastric cancer development and leading to poor immunotherapy.

CONCLUSIONS: High ACVR1 expression can be used as an independent prognostic factor to predict the prognostic survival of patients with gastric cancer. ACVR1 expression in gastric cancer tissues was significantly correlated with immune infiltration and may thus serve as a potential therapeutic target for gastric cancer immunotherapy.